1-209763382-A-G

Position:

• chr1-209763382-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025228.4(TRAF3IP3):​c.596A>G​(p.Asp199Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAF3IP3 NM_025228.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.20

Genes affected

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

TRAF3IP3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18404323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRAF3IP3	NM_025228.4	c.596A>G	p.Asp199Gly	missense_variant	7/17	ENST00000367025.8	NP_079504.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRAF3IP3	ENST00000367025.8	c.596A>G	p.Asp199Gly	missense_variant	7/17	1	NM_025228.4	ENSP00000355992.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 01, 2024

The c.596A>G (p.D199G) alteration is located in exon 7 (coding exon 5) of the TRAF3IP3 gene. This alteration results from a A to G substitution at nucleotide position 596, causing the aspartic acid (D) at amino acid position 199 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.037	T;T;.;T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.13
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.76	T;.;T;T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.18	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	.;N;.;N
PrimateAI	Uncertain	0.48	T
PROVEAN	Uncertain	-2.5	N;N;N;N
REVEL	Benign	0.043
Sift	Benign	0.12	T;T;T;T
Sift4G	Benign	0.69	T;T;T;T
Polyphen		0.0060	B;B;B;B
Vest4		0.19
MutPred		0.23		.;Loss of stability (P = 0.0959);.;Loss of stability (P = 0.0959);
MVP		0.42
MPC		0.20
ClinPred		0.50	T
GERP RS		4.5
Varity_R		0.11
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-209936727;